Immunization with gp120-depleted whole killed HIV immunogen and a second-generation CpG DNA elicits strong HIV-specific responses in mice

• Published in: Vaccine Vol. 24; no. 9; pp. 1470 - 1477
• Main Authors: Trabattoni, Daria, Clivio, Alberto, Bray, Dorothy H., Bhagat, Lakshmi, Beltrami, Silvia, Maffeis, Giada, Cesana, Eugenio, Lowry, Peter, Lissoni, Francesca, Kandimalla, Ekambar R., Sullivan, Timothy, Agrawal, Sudhir, Bartholomew, Richard, Clerici, Mario
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 27-02-2006; Elsevier Limited
• Subjects: AIDS Vaccines - administration & dosage; AIDS Vaccines - immunology; Animals; Cells, Cultured; Chemokine CCL3; Chemokine CCL4; Chemokine CCL5 - biosynthesis; Clinical trials; CpG; Cytokines; Deoxyribonucleic acid; DNA; Drug Therapy, Combination; Female; HIV; HIV Antibodies - blood; HIV Envelope Protein gp120; Human immunodeficiency virus; Human immunodeficiency virus 1; Immune system; Immunization; Immunogenicity; Immunology; Immunomodulatory oligonucleotide; Infections; Interferon-gamma - biosynthesis; Interleukin-5 - biosynthesis; Lymphocytes; Lymphocytes - immunology; Macrophage Inflammatory Proteins - biosynthesis; Mice; Mice, Inbred C57BL; Oligonucleotides - administration & dosage; Oligonucleotides - pharmacology; Proteins; Rodents; Studies; TLR9; Vaccine; Vaccines; Immunology; HIV; Cytokines; Immunomodulatory oligonucleotide; TLR9; Vaccine; CpG
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2005.05.047

HIV-1 Immunogen is a gp120-depleted whole killed virus vaccine candidate formulated with Incomplete Freund's Adjuvant (HIV-IFA). We evaluated in a mouse model the immunogenicity of HIV-IFA by itself and when combined with HYB2055, an immunomodulatory oligonucleotide consisting of a novel DNA structure and synthetic CpR immunostimulatory motif, as an adjuvant. C57/BL6 mice were immunized with HIV-IFA alone or combined with HYB2055. Mice treated with HYB2055 or with PBS were used as controls. Compared to HIV-IFA alone, immunization with HIV-IFA and HYB2055 combination elicited strong production of HIV- and p24-specific IFNγ, RANTES, MIP 1α, and MIP 1β, as well as high titers of HIV- and p24-specific antibodies. Inclusion of HYB2055 also reduced levels of IL-5 produced by HIV-IFA alone. HYB2055 enhances the immunogenicity of HIV-IFA and shifts responses towards a type 1 cytokine profile. The immune enhancing effects of HYB2055 adjuvant were dose-dependent. These findings warrant clinical evaluation of the HIV-1 immunogen/HYB2055 candidate as a therapeutic vaccine for HIV-1 infected patients.